Carbohydrate-protein macromolecules found in cardiovascular (CV) structures are basic connective tissue components that play an important role in maintaining the integrity of the CV system. These CV connective tissue macromolecules are involved in a variety of diseases of the heart and blood vessels. A major interest of these studies concerns proteoglycans of the arterial wall matrix. Characterization of two types of proteoglycan materials from aorta that have been isolated are in progress. A hybrid chondroitin sulfate-dermatan sulfate proteoglycan is closely linked with collagen and a heparan sulfate proteoglycan is associated with elastin. 35S uptake of aorta tissue proteoglycans show a high specific activity of the dermatan sulfate chains, although a greater release rate of the heparan sulfate proteoglycans from aorta cells is suggested. Interaction studies of the chondroitin sulfate-dermatan sulfate proteoglycan with serum lipoproteins indicate the core protein and the side chains of glycosaminoglycans are both essential in these interactions. An interaction with serum lipoproteins occurs at a much lower concentration than with glycosaminoglycans alone. The interaction noted between plasma low and very low density lipoproteins (LDL & VLDL) and the arterial wall proteoglycans suggest an entrapment of serum lipoproteins as a mechanism of developing atherosclerosis. This complexing of lipoproteins and proteoglycans are being explored in experimental models of high fat-cholesterol feedings; observations in rabbits indicate newly retained 125I LDL is mainly bound to the free proteoglycans in atherosclerotic lesions, with a considerable increase of LDL uptake by elastin. These studies are important in exploring mechanisms of atherogenesis.